title: Enoxaparin reduces adrenergic contraction of resistance arterioles in aging and in aging associated with diabetes via engagement of MAP kinase pathway.
abstract: The arterial endothelial dysfunction in aging and diabetes remains a clinical problem. We questioned the effect of the low-molecular-weight heparin, enoxaparin, on arterioles contractility in aging and in aging associated with diabetes, and investigated the involvement of the mitogen-activated protein (MAP) kinases pathway in the enoxaparin-mediated effect. The experiments were performed on the isolated resistance arteries of young (4 months old), aged (16 months old), and aged-diabetic hamsters (16 months old and 5 months since streptozotocin injection). The techniques used were myography, molecular biology, and immunoblotting. The results showed that 60 μg/ml enoxaparin has favorable effects on the arteriole reactivity in aged and aged-diabetic conditions, reducing the contractile response to 10-10 mol/l noradrenaline. The diminishment of contractility is exerted via MAP kinase pathway, and involves reduction of c-fos gene expression and of transcription factor AP-1 protein expression. These results suggest that enoxaparin preserves the arterial endothelial function in a mechanism independent of its anticoagulant activity. Understanding the signal transduction mechanisms involved in the altered contractility of vascular wall could provide useful information on the development of specific MAP kinase inhibitors with therapeutic benefits and reduced side effects.
authors.affiliation: Petru Poni Institute of Macromolecular Chemistry, Iasi, Romania. adriana.georgescu@icbp.ro
authors.forename: Adriana
authors.initials: A
authors.lastname: Georgescu
authors.forename: Nicoleta
authors.initials: N
authors.lastname: Alexandru
authors.forename: Miruna
authors.initials: M
authors.lastname: Nemecz
authors.forename: Irina
authors.initials: I
authors.lastname: Titorencu
authors.forename: Doina
authors.initials: D
authors.lastname: Popov
mesh_terms: D018663:Adrenergic Agents / Q000494:pharmacology; D000375:Aging; D000818:Animals; D001160:Arterioles / Q000187:drug effects* / Q000502:physiology; D006224:Cricetinae; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D017984:Enoxaparin / Q000494:pharmacology*; D015870:Gene Expression; D006801:Humans; D008297:Male; D008647:Mesocricetus; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D009213:Myography; D009638:Norepinephrine / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D046509:Tissue Culture Techniques; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*; D014655:Vascular Resistance / Q000187:drug effects*
chemical_list: D018663:Adrenergic Agents; D017984:Enoxaparin; D047428:Protein Kinase Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D018808:Transcription Factor AP-1; D020928:Mitogen-Activated Protein Kinases; D009638:Norepinephrine